New derivatives of 3-aminoindole. Synthesis of 2-aryl(hetaryl)-3-(3,5- dimethyl-1-pyrazolyl)indoles

Article abstract of DOI:10.1007/s10593-005-0060-4

The interaction of arylhydrazines with ω-(3,5-dimethyl-1-pyrazolyl) acetophenones and acetyl(2-thiophene) leads to arylhydrazones, which are converted by Fischer cyclization into 2-aryl(thienyl)-3-(3,3-dimethyl-1- pyrazolyl)indoles with substituents in positions 1, 5, and 7.

Full text of DOI:10.1007/s10593-005-0060-4

Chemistry of Heterocyclic Compounds, Vol. 40, No. 10, 2004
CHEMISTRY OF ACYL(IMIDOYL)KETENES.
8*. THERMOLYSIS OF 3-ALKOXYCARBONYL-
5-PHENYL-1,2,4,5-TETRAHYDROPYRROLO[1,2-a]-
QUINOXALINE-1,2,4-TRIONES. STRUCTURE OF
2-(3-OXO-4-PHENYL-3,4-DIHYDRO-2-QUINOXALINYL)-
2,4-DI(ETHOXYCARBONYL)-6-PHENYL-2,3,5,6-TETRAHYDRO-
1H-PYRIDO[1,2-a]QUINOXALINE-1,3,5-TRIONE
A. N. Maslivets1, Z. G. Aliev2, O. P. Krasnykh1, O. V. Golovnina1, and L. O. Atovmyan2
3-Alkoxycarbonylmethylene-1-phenyl-1,2,3,4-tetrahydro-2-quinoxalones, obtained by the interaction of
dialkyl esters of oxaloacetic acid and N-phenyl-o-phenylenediamine, react with oxalyl chloride with the
formation of 3-alkoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones.
Alkoxycarbonyl(2-oxo-1-phenyl-1,2-dihydro-3-quinoxalinyl)ketenes,
generated
on
thermal
decarbonylation of the latter, are stabilized by participation in a [4+2] cyclodimerization reaction with
the formation of 2,4-di(alkoxycarbonyl)-2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-6-phenyl-
2,3,5,6-tetrahydro-1H-pyrido[1,2-a]quinoxaline-1,3,5-triones. The crystal and molecular structure of
the di(ethoxycarbonyl) derivative have been investigated by X-ray structural analysis.
Keywords: alkoxycarbonyl(imidoyl)ketene, acyl(imidoyl)ketene, pyrroledione, crystal and molecular
structure, [4 + 2] cyclodimerization.
Two routes have been described for the stabilization of acyl(imidoyl)ketenes in which the imidoyl
fragment is part of a heterocyclic system.
Alkoxycarbonyl(2-oxo-1,2-dihydro-3-quinoxalinyl)ketenes A are cyclized intramolecularly as a result of
acylation of the hydroxy group of the tautomeric hydroxyimine form by the ketene fragment [2]. Aroyl(2-oxo-
3,4-dihydro-2H-1,4-benzoxazin-3-yl)ketenes B and aroyl(3-aryl-2-quinoxalinyl)ketenes C, in the absence of
partners for interaction, participates in a [4 + 2] cyclodimerization reaction [1,3,4]. The role of diene is played by
the imidoylketene fragment of one ketene molecule, and the role of dienophile by the C=C bond of the ketene
fragment of the other molecule. A [1,3]-migration of the aroyl group occurs in the [4 + 2] cycloadducts formed
initially.
The thermolytic conversion of 3-alkoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-
1,2,4-triones 2a,b has been investigated in the present work.
_______
* For Part 7 see [1].
__________________________________________________________________________________________
1
2
Perm State University, Perm 614000, Russia; e-mail: koh@psu.ru. Institute of the Problems of
Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Moscow region. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1501-1506, October, 2004. Original article submitted
April 2, 2002.
0009-3122/04/4010-1295©2004 Springer Science+Business Media, Inc.
1295

O
O
H
N
N
Ar
O
R
O
N
R = OAlk
R = Ar
C
O
A
B, C
N
N
OH
COAr
O
OAlk
N
O
O
COAr
C
O
N
[1,3]COAr
COAr
N
O
N
COOAlk
H
N
O
OCOAr
N
For alkoxycarbonyl(2-oxo-1-phenyl-1,2-dihydro-3-quinoxalinyl)ketenes 1a,b, generated by the thermal
decarbonylation of compounds 2a,b, an intramolecular cyclization of the type described above [2] is structurally
impossible and there are alternative possibilities for participation in intramolecular cycloaddition reactions for
both the alkoxycarbonylketene and the imidoylketene fragments. Synthesis of the pyrroloquinoxalinetriones
2a,b was carried out by the known method by the interaction of oxalyl chloride and
Z-3-alkoxycarbonylmethylene-1-phenyl-1,2,3,4-tetrahydro-2-quinoxalones 3a,b, obtained in turn, by the
reaction of dialkyl esters of oxaloacetic acid and N-phenyl-o-phenylenediamine.
On maintaining solutions of pyrroloquinoxalinetriones 2a,b in dowtherm A [5] at 185-187°C for 5-7 min
2,4-di(alkoxycarbonyl)-2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-6-phenyl-2,3,5,6-tetrahydro-1H-
pyrido[1,2-a]quinoxaline-1,3,5-triones 4a,b* are formed. The structure of the di(ethoxycarbonyl) derivative 4b
was identified on the basis of data of X-ray structural analysis.
Probably ketenes 1a,b, formed on thermal decarbonylation of pyrroloquinoxalinetriones 2a,b, are
stabilized by participating in a [4 + 2] cyclodimerization reaction analogously [1, 4]. The [1,3]-acylotropic shift
of alkoxycarbonyl groups, described in [1, 3, 4] for the aroyl analogs, does not occur in the resulting
cycloadducts 4a,b, probably as a result of their lower stability compared with the readily migrating aroyl groups.
_______
* See preliminary communication [6].
1296

NHPh
NH2
Ph
N
O
(COCl)2
AlkOCOCH2COCOOAlk
N
H
COOAlk
3a,b
Ph
N
O
Ph
N
Ph
N
COOAlk
O
N
O
O
OAlk
C
∆
O
COOAlk
O
N
–CO
O
N
N
COOAlk
C
O
N
Ph
O
O
2a,b
1a,b
4a,b
1–4 a Alk = Me, b Alk = Et
As a result of an X-ray structural investigation it became clear that specially grown crystals of compound
4b cocrystallized with benzene and water molecules in a ratio of 1:1:1. The general shape of the compound 4b
molecule is shown in Fig. 1. The tricyclic fragment of the molecule deviates significantly from a planar
structure. The pyrazine ring has a boat conformation. Twists along the line C(8)···C(11) and C(9)···C(10) were
19.8 and 13.2° respectively, and the deviations of the N(1) and N(2) atoms from the plane of the four carbon
atoms were 0.24 and 0.15 Å. The phenyl substituent at the N(2) atom has a strictly bisecting orientation. The
pyridine ring is also non-planar and has an envelope conformation. The twist along the N(1)···C(2) line was
28.6°. The deviation of the C(1) atom from the plane of the remaining five ring atoms was 0.37 Å to the side of
the quinoxaline substituent at the C(2) atom. The orientations of the ethoxycarbonyl groups are characterized by
Fig. 1 Structure of the compound 4b molecule.
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torsion angles C(3)C(4)C(5)O(4) of 72.7 and C(3)C(2)C(22)O(7) of 144.9°. The quinoxaline group at C(2) was
planar. The torsion angle C(3)C(2)C(25)N(3) was equal to 112.6° and the plane of the phenyl substituent at the
N(4) atom was orthogonal to the plane of the quinoxaline. The C(4)=C(8) and N(3)=C(25) double bonds
[1.350(3) and 1.273(3) Å respectively] were localized, without significant participation in conjugation. The
remaining bond lengths in the molecule have the usual values and require no comment.
Unlike the benzene molecule the water of crystallization molecule was randomized statistically at two
crystallographic positions. Since both these positions are close to the center of inversion with coordinates
0.5 0 0, the water molecule is in fact randomized statistically with a weighting of 1/4 at four positions at the
corners of a square with side 1.70 Å. Hydrogen bonds and other shortened contacts were absent from the crystal.
EXPERIMENTAL
The IR spectra of the synthesized compounds were recorded on a UR 20 spectrometer in nujol, the
1H NMR spectra on a Bruker DRX 400 (400 MHz) instrument in DMSO-d6, internal standard was HMDS
(δ 0.05 ppm), and the mass spectrum on a MX 1410 instrument with ionising voltage 70 eV. The homogeneity of
the obtained compounds was confirmed by TLC on Silufol plates in the system benzene–ethyl acetate, 5:1.
Z-3-Methoxycarbonylmethylene-1-phenyl-1,2,3,4-tetrahydro-2-quinoxalone (3a). A solution of
N-phenyl-o-phenylenediamine (10 mmol) in dioxane (15 ml) was added to a solution of oxaloacetic acid
dimethyl ester (10 mmol) in dioxane (5 ml). The mixture was boiled for 1 h 30 min, cooled, and the precipitated
solid compound 3a filtered off. Yield 2.65 g (90%); mp 194-195°C (dioxane). IR spectrum, ν, cm-1: 2980 br
1
(NH), 1680 (C(2)=O), 1612 br (COO). H NMR spectrum, δ, ppm: 3.71 (3H, s, CH3O); 5.59 (1H, s, CH);
6.25-7.95 (9H, m, C6H5 + C6H4); 11.15 (1H, s, NH). Found, %: C 69.40; H 4.83; N 9.45. C17H14N2O3.
Calculated, %: C 69.38; H 4.79; N 9.52.
Z-3-Ethoxycarbonylmethylene-1-phenyl-1,2,3,4-tetrahydro-2-quinoxalone (3b). Yield 2.62 g (85%);
mp 161-163°C (toluene). IR spectrum, ν, cm-1: 3015 br (NH), 1685 (C(2)=O), 1630 (COO). 1H NMR spectrum, δ,
ppm: 1.31 (3H, t, CH3); 4.21 (2H, q, CH2); 5.61 (1H, s, CH); 6.32 (1H, d, o-CH in C6H5); 6.81-7.69 (8H, m,
2C6H4); 11.22 (1H, s, NH). Found, %: C 70.07; H 5.18; N 9.14. C18H16N2O3. Calculated, %: C 70.12; H 5.23; N
9.09.
3-Methoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-trione (2a).
A
solution of compound 3a (10 mmol) and oxalyl chloride (10 mmol) in absolute chloroform (50 ml) was boiled
for 1 h, cooled, and the precipitated solid compound 2a filtered off. Yield 3.13 g (90%); mp 187-189°C
1
(chloroform). IR spectrum, ν, cm-1: 1770 (C(1)=O), 1750 (COO), 1730 (C(2)=O), 1690 (C(4)=O). H NMR
spectrum, δ, ppm: 3.74 (3H, s, CH3O); 6.69 (1H, d, o-CH in C6H5); 7.39-8.35 (8H, m, 2C6H4). Found, %:
C 65.50; H 3.51; N 8.01. C19H12N2O5. Calculated, %: C 65.52; H 3.47; N 8.04.
3-Ethoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-trione (2b). Yield 3.26 g
(90%); mp 185-187°C (chloroform). IR spectrum, ν, cm-1: 1765 (C(1)=O), 1725 (COO, C(2)=O), 1675 (C(4)=O).
1H NMR spectrum, δ, ppm: 1.31 (3H, t, CH3); 4.27 (2H, q, CH2); 6.56 (1H, d, o-CH in C6H5); 7.00-7.70 (7H, m,
C6H4 + C6H3); 7.85 (1H, d, o-CH in C6H5). Found, %: C 66.28; H 3.87; N 7.76. C20H14N2O5. Calculated, %:
C 66.30; H 3.89; N 7.73.
2,4-Di(methoxycarbonyl)-2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-6-phenyl-2,3,5,6-tetrahydro-
1H-pyrido[1,2-a]quinoxaline-1,3,5-trione (4a). A solution of compound 2a (1 mmol) in dowtherm A (4 ml)
was maintained at 185-187°C for 7 min, cooled, and the precipitated solid compound 4a filtered off.
Yield 0.33 g (52%); mp 235-237°C (decomp., from benzene). IR spectrum, ν, cm-1: 1740, 1720 (COOCH3),
1
1675 (CO). H NMR spectrum, δ, ppm: 3.30 (6H, s, 2CH3); 6.42-7.80 (18H, m, 2C6H5 + 2C6H4). Found, %:
C 67.48; H 3.77; N 8.72. C36H24N4O8. Calculated, %: C 67.50; H 3.78; N 8.75.
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2,4-Di(ethoxycarbonyl)-2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-6-phenyl-2,3,5,6-tetrahydro-
1H-pyrido[1,2-a]quinoxaline-1,3,5-trione (4b). A solution of compound 2b (1.66 mmol) in dowtherm A (4 ml)
was maintained at 185-187°C for 5 min, cooled, and the precipitated solid 4b filtered off. Yield 0.27 g (40%);
1
mp 209-211°C (decomp., from benzene). IR spectrum, ν, cm-1: 1720 (COOC2H5), 1645 (CO). H NMR
spectrum, δ, ppm, (J, Hz): 1.24 (3H, t, J = 7.0, CH3); 1.42 (3H, t, J = 7.0, CH3); 4.17 (2H, q, J = 7.0, CH2); 4.50
(2H, q, J = 7.0, CH2); 6.40-8.03 (18H, m, 2C6H5 + 2C6H4). Mass spectrum, m/z (I, %): 668 [M]+. Found, %:
C 68.31; H 4.25; N 8.41. C38H28N4O8. Calculated, %: C 68.26; H 4.22; N 8.38.
X-ray Structural Investigation of Compound 4b. For the X-ray structural investigation compound 4b
was repeatedly crystallized from aqueous benzene. The yellow well-defined crystals of C38H28N4O8·C6H6·H2O
were triclinic: a = 13.556(3), b = 17.452(3), c = 9.244(2) Å; α = 95.70(3), β = 104.29(3), γ = 100.28(3)°;
V = 2061.5(7) Å3; M = 764.77; Z = 2; dcalc = 1.232 g/cm3; space group P1. Unit cell parameters and the set of
experimental reflections were measured with an automatic 4-circle KM-4 diffractometer (Kuma Diffraction)
with CuKα radiation in the angle range 2.6 < θ < 80.3°. The structure was determined by the direct statistical
method. Hydrogen atoms were fixed geometrically. A full-matrix anisotropic (for non-hydrogen atoms)
refinement by the method of least squares was carried out to R = 0.0612 for 5041 reflections with I > 2σ(I) from
the overall group of 8498 reflections measured. GooF = 1.065. No corrections for absorption were introduced
(µ = 0.719 mm-1). All calculations were carried out with the SHELX-97 set of programs [7].
The work was carried out with the financial support of the Russian Fund for Fundamental Investigations
(project No. 01-03-32641).
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4.
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(2000).
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G. M. Sheldrick, SHELX-97. Programs for Crystal Structure Analysis, Univ. of Göttingen, Göttingen,
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